The vitamin E long-chain metabolite α-13′-COOH affects macrophage foam cell formation via modulation of the lipoprotein lipase system

In vitro and In vivo oxidation and cleavage products of tocols: From chemical tuners to “VitaminEome” therapeutics. A narrative review

“…In a more recent report, α-13′-COOH revealed possible antiatherogenic effects via the modulation of the lipoprotein lipase system which reduced VLDL-induced foam cell formation in THP-1 macrophages (Kluge et al, 2021). These metabolites, including Garcinoic acid (δ-T3-13′-COOH), were also inhibitors of lipopolysaccharide-stimulated inducible nitric oxide synthase (iNos) expression and Cox 2 in murine RAW264.7 macrophages Ciffolilli et al, 2015;Schmölz et al, 2017;Wallert et al, 2019).…”

Vitamin E in foodstuff: Nutritional, analytical, and food technology aspects

“…α‐13ʹ‐COOH has been recently shown to be capable of inducing lipid storage capacity and thereby reducing susceptibility to lipotoxicity (Schmölz et al., 2018). Moreover, α‐13′‐COOH can induce the post‐translational regulation of LPL via angiopoietin‐like 4 and protect macrophages from excessive lipid accumulation in the presence of surplus VLDL (Kluge et al., 2021). To date, most studies have been conducted in vitro.…”

Vitamin E and Metabolic Health: Relevance of Interactions with Other Micronutrients

“…The resulting metabolites are the long-chain metabolites (LCM), namely, the initially formed 13’-tocopherol-hydroxychromanol (13’-OH) and the subsequently formed 13’-tocopherol-carboxychromanol (13’-COOH). Thereinto, 13’-COOH has emerged as a derivate of vitamin E with many regulatory functions, revealing superior and sometimes even different effects compared to its metabolic precursor [ 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. The following β-oxidation shortens the side-chain of the LCM and results in the formation of several intermediate-chain metabolites (ICM) and, finally, the short-chain metabolite (SCM) of vitamin E, namely, CEHC or 3’-COOH.…”

“…Our group has shown that α-13’-COOH protects THP-1 macrophages from stearic acid-induced lipotoxicity by increasing the expression of the lipid droplet-associated protein (PLIN2, adipophilin), in contrast to its precursor α-TOH which exerts opposite effects [ 34 ]. Recently, Kluge et al [ 35 ] reported that α-13’-COOH reduces foam cell formation of human THP-1 macrophages via an increase in the expression and release of angiopoietin-related protein 4 (ANGPTL4), which reduces TG hydrolysis from TG-rich lipoproteins such as very-low-density lipoproteins (VLDL) by inhibiting lipoprotein lipase (LPL) activity.…”

“…Recent findings revealed that the LCMs have several similarities to vitamin E as regulatory molecules. However, for some effects, such as the regulation of cellular lipid homeostasis [ 31 , 34 , 35 ] or the modulation of the inflammatory response [ 196 ], the LCMs showed superior or even different effects compared to its precursors. For that reason, it has been proposed that the metabolic activation is a premise for the functional properties of vitamin E in humans [ 27 , 188 ].…”